Preparation of maleimides



United States Patent 3,018,292 PREPARATION OF MALEIMIDES Carol K. Sauers, Middlebush, and Robert J. Cotter, New

Brunswick, NJ., assignors to Union Carbide Corporation, a corporation of New York No Drawing. Filed Nov. 12, 1959, Ser. No. 852,231 7 Claims. (Cl. 260-3265) This invention relates to the preparation of maleimides. More particularly, this invention relates to the preparation of N-substituted maleimides by the cyclodehydration of the corresponding maleamic acid.

The preparation of maleimides has been accomplished, generally, by the cyclodehydration of the corresponding maleamic acids by heating a mixture of the desired maleamic acid, acetic anhydride, and either potassium or sodium acetate at a temperature of about 80 C. with the result that the maleamic acid is dehydrated, yielding the corresponding maleimide. This method, although satisfactory for the preparation of N-aryl substituted maleimides, such as N-phenyl maleimide, is not satisfactory for the preparation of N-aliphatic substituted maleimides, such as N-n-butyl maleimide. N-alip'hatic substituted maleimides prepared by such a process have been low in yield and usually contains large quantities of undesirable resinous by-products.

The present invention provides for the preparation of N-substituted maleimides, including N-aliphatic substituted maleimides, in satisfactory yields and without the substantial formation of undesirable resinous by-products by admixing an N-substituted maleamic acid, an organic tertiary amine, and an acyl halide having a maximum of four carbon atoms, whereby the N-substituted maleamic acid is cyclodehydrated to the corresponding maleimide.

Illustrative of N-substituted maleamic acids which can be cyclodehydrated in accordance with the present invention are those having the general formula:

in which R is a monovalent hydrocarbon radical or a divalent hydrocarbon radical having as a substituent on its terminal carbon atom a radical having the formula:

These latter N-substituted maleamic acids are commonly referred to as bis-maleamic acids.

The term monovalent hydrocarbon radical as used herein is intended to encompass unsubstituted hydrocarbon radicals as well as substituted hydrocarbon radicals.

Exemplary of such radicals are alkyl radicals, such as methyl, ethyl, n-propyl, n-butyl, n-hexyl, 2-ethyl-n-hexyl, n-octyl, n-dodecyl, and the like; cycloalkyl radicals, such as cyclohexyl and the like; unsaturated alkyl and cycloalkyl radicals, such as allyl, cyclopentenyl, and the like; halogenated alkyl and cycloalkyl radicals, such as chloromethyl, bromomethyl, fluoromethyl, Z-chloro-n-propyl, 2- bromo-n-propyl, 2-chloro-n-butyl, 3-chloro-n-amyl, 3- bromo-n-amyl, l-chloro-n-hexyl, 2-chlorocyclohexyl, and the like; alkoxy and aryloxy substituted alkyl and cycloalkyl radicals, such as methoxymethyl, ethoxyethyl, 3- ethoxy-n-propyl, 4-ethoxy-n-butyl, 3-ethoXy-2-ethyl-nhexyl, Z-methoxycyclohexyl, phenoxymethyl, Z-phenoxyethyl, 3-phenoxy-n-propyl, Z-phenoxycyclohexyl, and the like; aralkyl radicals, such as benzyl, Z-phenylethyl, 3-

2 phenyl-n-propyl, l-phenyl-n-butyl, l-phenyl-n-docesyl, and the like; aryl radicals, such as phenyl, naphthyl, and the like; halogenated aryl radicals, such as p-chlorophenyl, p-bromophenyl, p-fluorophenyl, p-iodophenyl, 2-chlorm naphthyl, 2-bromonaphthyl, and the like; alkoxy and aryloxy substituted aryl radicals, such as p-methoxyphenyl, pethoxyphenyl, p-n-propoxyphenyl, and the like; alkaryl radicals, such as p-methylphenyl, pethylphenyl, p-n-propylphenyl, o-n-propylphenyl, o-n-butylphenyl, p-n-dodecylphenyl, p-(Z-ethyl-n-hexyl) phenyl, and the like; nitro substituted aryl radicals, such as p-nitrophenyl, 2-nitronaphthyl, and the like; other suitable radicals include 4- hydroxynaphthyl, and the like.

Representative of maleamic acids wherein R in the general formula previously given in a monovalent hydro carbon radical are N-methyl maleamic acid, N-ethyl maleamic acid, N-n-propyl maleamic acid, N-allyl maleamic acid, N-n-butyl maleamic acid, N-tertiary butyl maleamic acid, N-n-hexyl maleamic acid, N-(Z-ethyl-n-hexyl) maleamic acid, N-n-heptyl maleamic acid, N-n-nonyl maleamic acid, N-n-dodecyl maleamic acid, N-n-decosyl maleamic acid, N-cyclohexyl maleamic acid, N-(Z-chloroethyl) maleamic acid, N-(2-bromoethyl) maleamic acid, N-(2- fluoroethyl) maleamic acid, N-(Z-iodo-n-propyl) maleamic acid, N-(2-chlorohexyl) maleamic acid, N-methoxymethyl maleamic acid, N-benzyl maleamic acid, N-(2- phenylethyl) maleamic acid, N-(B-phenylpropyl) maleamic acid, N-(4-phenyl-n-butyl) maleamic acid, N-phenyl maleamic acid, N-naphthyl maleamic acid, N-(o-chlorophenyl) maleamic acid, N-(m-bromophenyl) maleamic acid, N-(p-fiurophenyl) maleamic acid, N-(o-iodophenyl) maleamic acid, N-(o-methoxyphenyl) maleamic acid, N- (m-methoxyphenyl) maleamic acid, N-(p-ethoxyphenyl) maleamic acid, N-(p-n-butoxyphenyl) maleamic acid, N- (p-chloro-m-methylphenyl) maleamic acid, N-(o-methylphenyl) maleamic acid, N-(m-methylphenyl) maleamic acid, N-(o-ethylphenyl) maleamic acid, N-(m-ethylphenyl) maleamic acid, N-(p-ethylphenyl) maleamic acid, N- (o-isopropylphenyl) maleamic acid, N-(m-isopropylphenyl) maleamic acid, N-(p-isopropyl phenyl) maleamic acid, N-(o-n-butylphenyl) maleamic acid, N-(m-n-butylphenyl) maleamic acid, N-p-tolyl maleamic acid, N-(4-hydroxy-lnaphthyl) maleamic acid, and the like.

The term divalent hydrocarbon radicals as used herein is intended to encompass both unsubstituted as well as substituted divalent hydrocarbon radicals. Illustrative of suitable radicals are alkylene radicals, such as ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, 2-ethyl hexamethylene, octamethylene, nonamethylene, decamethylene, and the like; the cycloaliphatic radicals, such as 1,4-cycl0hexane, 1,3-cyclohexane, 1,2-cyclohexane, and the like; halogenated alkylene and cycloaliphatic radicals, such as 2-chloroethylene, 2- bromoethylene, 2-fluoroethylene, 2-iodoethylene, 2-chlorotrimethylene, 2-bromotrimethylene, 2-chloropentamethylene, 3-chlorohexamethylene, Z-chloro-octamethylene, and the like; alkoxy and aryloxy substituted alkylene and cycloaliphatic radicals, such as methoxymethylene, ethoxymethylene, ethoxyethylene, Z-ethoxytrimethylene, 3 ethoxypentamethylene, 1,4-(Z-methoxycyclohexane), Z-phenoxyethylene, Z-phenoxytrimethylene, 1,3-(2-phenoxycyclohexane), and the like; aralkylene radicals, such as 2-phenylethylene, 2-phenyltrirnethylene, l-pheuylpentamethylene, Z-phenyldecamethylene, and the like; aro matic radicals, such as phenylene, naphthylene, and the like; halogenated aromatic radicals, such as 1,4-(2-chlorophenylene), 1,4-(2-bromophenylene), 1,4-(2-fiuorophenylene), and the like; alkoxy and aryloxy substituted aromatic radicals, such as 1,4-(2-rnethoxyphenylene), 1,4 (Z-ethoxyphenylene), 1,4-(Z-n-propoxyphenylene), 1,4- (Z-phenoxyphenylene), and the like; alkyl substituted aromatic radicals, such as 1,4-(2-methylphenylene), 1,4-

. 3 (2-ethylphenylene), l,4-(2-n-propylphenylene), 1,4-(2-nbuty-lphenylene), l,4-(Z-n-dodecylphenylene), and the like.

Among N-substituted maleamic acids wherein R in the formula previously noted is a divalent hydrocarbon radi cal having as a substituent on its terminal carbon atom a radical having the formula:

can be noted N,N'-ethylene bis maleamic acid, N,N-trimethylene bis-maleamic acid, N,N'-tetramethylene bismaleamic acid, N,N-decamethylene bis-maleamic acid, N,N-l,4-cyclohexane bis-maleamic acid, N,N'-2-chlorotrimethylene bis-maleamic acid, N,N'-2-bromotrimethylene bis-maleamic acid, N,N'-2-chlorotetramethylene bismaleamic acid, N,N-3-chlorohexamethylene bis-maleamic acid, N,N'-2-ethoxytetramethylene bis-maleamic acid, N,N'-2-ethoxytetramethylene bis-maleamic acid, N,N- l,4-(2-methoxycyclohexane) bis-maleamic acid, N,N'- phenoxyethylene bis-maleamic acid, N,N'-2-phenoxytrimethylene bis-maleamic acid, N,N-1,4-(2-phenoxycyclohexane) bis-maleamic acid, N,N'-l,4-(2-nitrocyclohexane) bis-maleamic acid, N,N-phenylmethylene bis-maleamic acid, N,N-phenylethylene bis-maleamic acid, N,N- 2-phenyltrimethylene bis-malearnic acid, N,N'-2-phenyltetramethylene bis-maleamic acid, N,N'-l-phenyldodecamethylene bis-maleamic acid, N,N-l,4-phenylene bismaleamic acid, N,N'-l,5-naphthalene bis-maleamic acid, N,N'-l,4-(2-chlorophenylene) bis-maleamic acid, N,N'- l,4(2bromophenylene) bis-maleamic acid, N,N'-l,4-(2- rnethoxyphenylene) bis-maleamic acid, N,N'-1,4-(2- ethoxyphenylene) bis-m'aleamic acid, N,N'-1,4-(2-phenoxyphenylene) bis-maleamic acid, N,N-1,4-(2-methylphenylene) bis-malearnic acid, N,N'-1,4-(2-ethylphenylene) bis-maleamic acid, N,N'-1,4-(2-n-propylphenylene) 'bis-maleamic acid, N,N-4,4'-(diphenyl ether) bis-maleamic acid, N,N'-1,4'-(2-n-dodecylphenylene) bis-maleamic acid, N,N'-4,4'-benzophenone bis-maleamic acid, and the like.

Particularly desirable compounds for purposes of this invention are those wherein R is either a monovalent or divalent radical as previously described having a maximum of 20 carbon atoms and being free of interfering groups. such as -COOH and NH Among suitable tertiary amines for purposes of this invention are those having the general formula:

wherein R is -a hydrocarbon radical free of ethylenic and acetylenic unsaturation. Illustrative of suitable radicals for R can be noted methyl, ethyl n-propyl, isopropyl, n-butyl, n-amyl, n-hexyl, 2-ethyl-n-hexyl, n-heptyl,n-octyl, n-nonyl, n-dodecyl, benzyl, 2-phenylethyl, 3-phenyl-npropyl, 4-phenyl-n-butyl, 5-phenyl-n-amyl, 2-phenyl-nhexyl, 3-phenyl-n-heptyl, phenyl, o-methylphenyl, p-ethylphenyl, p-amylphenyl, o-n-butylphenyl, and the like. Specific compounds include, among others, tn'methylamine, triethylamine, trim-propylamine, tri-n-butylamine, tri-namylamine, tri-(2-ethyl-n-hexyl) amine, tri-n-dodecylamine, tri-(Z-phenylethyl) amine, tribenzylamine, dimethyl propylamine, dimethyl-n-propylamine, methyl ethyl-n-propylamine, N,N-dimethylaniline, and the like. Particularly desirable compounds are those wherein the R is either an alkyl or an aralkyl radical having a maximum of 20 carbon atoms.

Suitable acyl halides for purposes of the present invention are those having the general formula:

wherein R is an alkyl group having a maximum of three carbon atoms and X is a halogen atom, i.e., chlorine, bro- N-n-butyl maleamic acid OKs-(13:0 2 s)a acetyl chloride triethyl amine 41in, +NH(CQH5)3 01+ ivmcmm (31330 N-n-butyl maleimide Various amounts of the starting materials can be used for purposes of the present invention. Generally from about a stoichiometric amount to about 5 times the stoichiometric amount of an acyl halide can be used. Using more than about 5 t lnes the stoichiometric amount does not materially increase the yield of N-substituted maleimide and is economically unattractive. For purposes of stoichiometric calculations, 1 molecule of an acyl halide is deemed to react with one -COOH group of the N-substituted maleamic acid. A mole ratio of about 2 to about 10' moles of an organic tertiary amine per mole of the N-substituted maleamic acid is satisfactory for purposes of the present invention. More than 10 moles of an organic tertiary amine per mole of N-substituted maleamic acid can be used if desired. Using more than about 10 moles per mole of the acid does not materially increase the yield of N-substituted maleimide and is therefore economically undesirable.

The temperature at which the N-su-bstituted maleamic acid can be cyclodehydrated can vary over a wide range, from about room temperature, i.e., about 25 C. to a temperature below the decomposition point of the reactants and of the maleimide product formed. At temperatures lower than about 25 C., the reaction proceeds sluggishly.

It is also preferred to conduct the cyclodehydration reaction in the presence of an organic diluent which is a solvent for the starting material and is non-reactive with the starting materials and the final product. Using an organic diluent facilitates recovery of the N-substituted maleimide from the reaction mixture.

The actual organic diluent used will depend upon the starting materials and the temperature at which the reaction is to be conducted. The organic diluent should have a boiling point above the reaction temperature. It is customary to use the organic diluent in amounts of at least about 50% by weight based on the weight of the starting materials. The upper limit with respect to the amount of organic diluent used will depend upon the rate at which it is desired to conduct the reaction. The more dilute the reaction mixture, the slower the rate of reaction. From a practical standpoint, the organic diluent is used in amounts up to about 500% by weight based on the weight of the starting materials.

Suitable organic diluents include, among others, the aromatic hydrocarbons, such as benzene, xylene, and the like; the halogenated aromatic hydrocarbons, such as chlorobenzene and the like; cycloaliphatic hydrocarbons, such as cyclohexane, n-propyl cyclohexane, and the .like; alkoxy substituted aromatic hydrocarbons, such as methoxybenzene and the like; aliphatic hydrocarbons, such as nhexane, n-heptane, and the like; halogenated aliphatic hydrocarbons, such as dichloromethane, 1,2-dichloroethane, and the like; ethers, such as petroleum ether, diethyl ether, diethyl ether of ethylene glycol, diethyl ether of 1,3-propylene glycol, dioxane, and the like; aliphatic ketones, such as acetone, methyl ethyl ketone, and the like; also suitable is dimethyl formamide, and the like.

The cyclodehydration of N-substituted maleamic acids is conducted, generally, under atmospheric pressure, although if desired, the reaction can be conducted under subatmospheric or superatmospheric pressure.

The process of the present invention is conducted by simply admixing the N-substituted maleamic acid, the organic tertiary amine and the acyl halide. The cyclodehydration of the N-substituted maleamic acid is practically instantaneous in that some N-substituted maleimide is formed immediately upon admixing of the necessary starting materials. It is customary, however, to allow the reaction mixture to stand for at least one hour in order to insure that the reaction has proceeded to completion.

Recovery of N-substituted maleimides from the reaction mixture can be accomplished by any one of a number of convenient methods. For example, in those instances wherein there is no diluent present in the reaction mixture or if a diluent is present, it is miscible with water, the reaction mixture can be poured into water with the result that the N-substituted maleimide separates out of the resultant water mixture. If the N-substituted maleimide is a solid, it can then be recovered by a simple filtration operation and then, if desired, recrystallized from suitable liquids, such as the organic liquids previously noted in this specification as organic diluents. If the N-substituted maleimide is a liquid, it can then be removed from the resultant water-mixture by extraction using a suitable organic solvent and recovered by evaporation of the solvent.

In those instances wherein the organic diluent is immiscible with water, the N-substituted maleimide formed is recovered by simply evaporating ofi the organic diluent.

If desired, the N-substituted maleimide can also be Washed with aqueous solutions of sodium bicarbonate, sodium hydroxide, and the like, or passed through column of Florisil in order to insure removal of unreacted starting materials.

The N-substituted maleamic acid intermediates which can be used in the preparation of the corresponding maleimides in accordance with the present invention can be obtained by reacting, in suitable solvents, approximately equimolar quantities of a primary monoor primary diamine with maleic anhydride. In producing an N-substituted maleamic acid having the formula previously given wherein R is a monovalent hydrocarbon radical, the following primary monoamines can be used: methylamine, ethylamine, isopropylamine, n-butylamine, isobutylamine, isoamylamine, n-hexylamine, n-heptylamine, n-octylamine, n-dodecylamine, cyclohexy-lamine, 2- chloroe'thylamine, 2-bromoethylamine, 2-fluoroethylamine, Z-iodopropylamine, chlorocylohexylamine, methoxymethylamine, 2-phenoxy-n-propylamine, benzylamine, 2-phenethylamine, 3-phenylpropyl-amine, 4-phenylbutylamine, naphthylarnine, p-toluidine, o-p--xylylidine, o-ethylaniline, m-ethylaniline, p-ethylaniline, o-isopropylaniline, m-isopropylaniline, p-isopropylaniline, o-n-butylaniline, m-n-butylan-iline, p-n-butylaniline, p-n-octylaniline, o-chloroaniline, n-bromoaniline, p-fiuoroaniline, o-iodoaniline, o-methoxyaniline, m-methoxyaniline, p-ethoxyaniline, p-n-butoxyan-iline, o-nitroaniline, p-nitroaniline, 4-chloro-3-methylaniline, o-toluidine, m-toluidine, 4-sulfamylaniline, and the like. In producing an N-substituted maleamic acid having the formula previously given wherein R is a divalent hydrocarbon radical, the following diamines can be used: 1,2-diam-inoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 1,4- phenylene diamine, 4,4-diaminodiphenylmeth-ane, and the like. Procms for producing maleamic acids is fur- 6 ther described in the book entitled Maleic Anhydride Derivatives by L. A. Flett and W. H. Gardner, incorporated by reference.

The following example further illustrates the present invention and is not intended to limit the scope thereof in any manner.

EXAMPLE 1 Preparation of N-n-butyl maleimide Into a Pyrex glass flask equipped with a stirrer, thermometer, dropping funnel, and reflux condenser contain, ing 200 ml. of diethyl ether there was charged 17.3 grams (0.1 mole) of N-n-butyl maleamic acid and 21 grams (0.21 mole) of triethylamine. 7.8 grams (0.1 mole) of acetyl chloride were slowly added to the mixture with constant stirring. The reaction mixture was allowed to stand at 25 C. for 16 hours While it Was being continuously stirred. The mixture was then filtered, removing triethylamine hydrochloride formed in the reaction mixture as a filter cake. The diethyl ether was removed from the filtrate under reduced pressure. The liquid product remaining 'was taken up in 200 ml. of benzene and washed in a separatory funnel with successive portions of 1 00 ml. of a 10% aqueous sodium hydroxide solution and water. The organic layer was separated from the water layer and the benzene removed therefrom under reduced pressure. The liquid residue Was distilled at a temperature of 50 C.-55 C. and at a pressure of 0.5 mm. Hg yielding 6 grams of a clear liquid distill-ate. The liquid product was shown to be N-n-bu-tyl maleimide by infra-red and vapor phase chromatographic analysis on comparison with known samples of N-n-butyl maleimide.

What is claimed is:

1. Process for the preparation of an N-substituted maleimide which comprises admixing an N-substituted maleamic acid of the formula:

wherein R is selected from the group consisting of a monovalent hydrocarbon radical and a divalent hydrocarbon radical having as a substituent on its terminal carbon atom a radical of the formula:

1? HOCOH a r with at least about 2 moles of an organic tertiary amine of the formula (R') N wherein R is a hydrocarbon radical free of olefinic and acetlylenic unsaturation, per mole of said maleamic acid and with at least about a stoichiometric amount of an acyl halide of the formula: R2(|J=O X wherein R is an alkyl radical having a maximum of three carbon atoms and X is a halogen atom, for a period of time sufiicient to produce the corresponding N-substituted maleimide.

2. Process as defined in claim 1 wherein the acyl halide is acetyl chloride.

3. Process as defined in claim 1 wherein the organic tertiary amine is triethylamine.

4. Process as defined in claim 1 wherein the maleamic acid is N-n-butyl maleamic acid.

5. Process as defined in claim 1 wherein the admixing is conducted at a temperature of from about 25 C. to a temperature below the decomposition point of the starting materials and the N-substituted maleimide formed.

6. Process for the preparation of an N-substituted male- 7 imide which comprises admixing in an organic diluent and at a temperature of from about 25 C. to a temperature below the decomposition temperature of the starting materials and the N-substituted maleimide formed, an N-substituted maleamic acid of the formula:

radical having as a substituent on its terminal carbon atom a radical of the formula:

with from about 2 moles to about 10 moles of an organic 8 tertiary amine of the formula (R) N wherein R is a hydrocarbon radical free of olefinic and acetylenic unsaturation, per mole of said maleamic acid and with from about a stoichiometric amount to about 5 times the stoichiometric amount of an acyl halide of the formula:

wherein R is an alkyl radical having a maximum of three carbon atoms and X is a halogen atom, for a period of time sufficient to produce the corresponding N-substituted maleimide.

7. Process as defined in claim 1 wherein the organic tertiary amine is present in an amount of from about 2. to about 10 moles per mole of said maleamic acid and the acyl halide is present in an amount of from about 2 to about 5 times the stoichiometric amount.

References Cited in the file of this patent UNITED STATES PATENTS 2,643,258 Miller et a1 June 23, 1953 

1. PROCESS FOR THE PREPARATION OF AN N-SUBSTITUTED MALEIMIDE WHICH COMPRISES ADMIXING AN N-SUBSTITUTED MALEAMIC ACID OF THE FORMULA:
 4. PROCESS AS DEFINED IN CLAIM 1 WHEREIN THE MALEAMIC ACID IS N-N-BUTYL MALEAMIC ACID. 